DE102004032567A1 - Substituierte 1-Propiolyl-piperazine - Google Patents
Substituierte 1-Propiolyl-piperazine Download PDFInfo
- Publication number
- DE102004032567A1 DE102004032567A1 DE102004032567A DE102004032567A DE102004032567A1 DE 102004032567 A1 DE102004032567 A1 DE 102004032567A1 DE 102004032567 A DE102004032567 A DE 102004032567A DE 102004032567 A DE102004032567 A DE 102004032567A DE 102004032567 A1 DE102004032567 A1 DE 102004032567A1
- Authority
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- Germany
- Prior art keywords
- group
- unsubstituted
- radical
- monosubstituted
- phenyl
- Prior art date
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- 239000003814 drug Substances 0.000 claims abstract description 55
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 230000008569 process Effects 0.000 claims abstract description 7
- -1 halogen radical Chemical class 0.000 claims description 574
- 125000005842 heteroatom Chemical group 0.000 claims description 87
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 85
- 150000003254 radicals Chemical class 0.000 claims description 76
- 229920006395 saturated elastomer Polymers 0.000 claims description 51
- 125000004419 alkynylene group Chemical group 0.000 claims description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims description 48
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 45
- 125000004450 alkenylene group Chemical group 0.000 claims description 45
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 45
- 239000001301 oxygen Substances 0.000 claims description 45
- 229910052760 oxygen Inorganic materials 0.000 claims description 45
- 239000011593 sulfur Substances 0.000 claims description 45
- 229910052717 sulfur Inorganic materials 0.000 claims description 45
- 125000002950 monocyclic group Chemical group 0.000 claims description 44
- 125000002947 alkylene group Chemical group 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
- 239000000460 chlorine Substances 0.000 claims description 41
- 229910052801 chlorine Inorganic materials 0.000 claims description 41
- 229910052794 bromium Inorganic materials 0.000 claims description 39
- 229910052731 fluorine Inorganic materials 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 34
- 208000002193 Pain Diseases 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 229940079593 drug Drugs 0.000 claims description 25
- 229910052740 iodine Inorganic materials 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 125000003277 amino group Chemical group 0.000 claims description 24
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 24
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 23
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 22
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims description 21
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims description 21
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 21
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- 239000000203 mixture Substances 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 18
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 229960002715 nicotine Drugs 0.000 claims description 18
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 17
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- 238000011282 treatment Methods 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 238000011321 prophylaxis Methods 0.000 claims description 16
- 206010013663 drug dependence Diseases 0.000 claims description 15
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
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- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 claims description 11
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 11
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 11
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 11
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 11
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 claims description 10
- 125000006017 1-propenyl group Chemical group 0.000 claims description 10
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 10
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 10
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 10
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 10
- 125000001931 aliphatic group Chemical group 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 10
- 229920002554 vinyl polymer Polymers 0.000 claims description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- 208000000094 Chronic Pain Diseases 0.000 claims description 9
- 125000003725 azepanyl group Chemical group 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000005959 diazepanyl group Chemical group 0.000 claims description 9
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 0.000 claims description 9
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
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- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
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- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 9
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- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
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- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 239000012429 reaction media Substances 0.000 claims description 9
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- 208000005298 acute pain Diseases 0.000 claims description 8
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
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- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 7
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- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 7
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
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- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 6
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- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
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Landscapes
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
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- Nutrition Science (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Child & Adolescent Psychology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
Priority Applications (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004032567A DE102004032567A1 (de) | 2004-07-05 | 2004-07-05 | Substituierte 1-Propiolyl-piperazine |
| AT05756539T ATE460413T1 (de) | 2004-07-05 | 2005-07-05 | Substituierte 1-propinoyl-piperazine mit affinität für den mglur5 rezeptor zur behandlung von schmerzzuständen |
| JP2007519700A JP5022218B2 (ja) | 2004-07-05 | 2005-07-05 | 置換１−プロピオリルピペラジン |
| PCT/EP2005/007248 WO2006002981A1 (de) | 2004-07-05 | 2005-07-05 | Substituierte 1-propiolyl-piperazine mit affinität für den mglur5 rezeptor zur behandlung von schmerzzuständen |
| PL05756539T PL1765816T3 (pl) | 2004-07-05 | 2005-07-05 | Podstawione propiolilopiperazyny o powinowactwie do receptora MGLUR5, do leczenia stanów bólowych |
| SI200531017T SI1765816T1 (sl) | 2004-07-05 | 2005-07-05 | Substituirani 1-propiolil-piperazini z afiniteto za MGLUR5 receptor za zdravljenje bolečih stanj |
| DE502005009201T DE502005009201D1 (de) | 2004-07-05 | 2005-07-05 | Substituierte 1-propinoyl-piperazine mit affinität für den mglur5 rezeptor zur behandlung von schmerzzuständen |
| PT05756539T PT1765816E (pt) | 2004-07-05 | 2005-07-05 | 1-propiolil-piperazinas substituídas com afinidade para o receptor mglur5 utilizadas no tratamento de condições de dor |
| EP05756539A EP1765816B1 (de) | 2004-07-05 | 2005-07-05 | Substituierte 1-propinoyl-piperazine mit affinität für den mglur5 rezeptor zur behandlung von schmerzzuständen |
| ES05756539T ES2342473T3 (es) | 2004-07-05 | 2005-07-05 | 1-propiolilpiperazinas sustituidas con afinidad por el receptor mglur5 para el tratamiento de estados de dolor. |
| CA002572685A CA2572685A1 (en) | 2004-07-05 | 2005-07-05 | Substituted 1-propiolylpiperazines compounds |
| DK05756539.2T DK1765816T3 (da) | 2004-07-05 | 2005-07-05 | Substituerede 1-propinylpiperaziner med affinitet for MGluR5-receptoren til behandling af smertetilstande |
| US11/649,156 US7300939B2 (en) | 2004-07-05 | 2007-01-04 | Substituted 1-propiolylpiperazine compounds, their preparation and use |
| CY20101100485T CY1110127T1 (el) | 2004-07-05 | 2010-06-03 | Υποκατεστημενες 1-προπιολυλο-πιπεραζινες με χημικη συγγενεια για τον υποδοχεα mglur5 για τη θεραπεια καταστασεων πονου |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004032567A DE102004032567A1 (de) | 2004-07-05 | 2004-07-05 | Substituierte 1-Propiolyl-piperazine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE102004032567A1 true DE102004032567A1 (de) | 2006-03-02 |
Family
ID=34971564
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102004032567A Withdrawn DE102004032567A1 (de) | 2004-07-05 | 2004-07-05 | Substituierte 1-Propiolyl-piperazine |
| DE502005009201T Active DE502005009201D1 (de) | 2004-07-05 | 2005-07-05 | Substituierte 1-propinoyl-piperazine mit affinität für den mglur5 rezeptor zur behandlung von schmerzzuständen |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE502005009201T Active DE502005009201D1 (de) | 2004-07-05 | 2005-07-05 | Substituierte 1-propinoyl-piperazine mit affinität für den mglur5 rezeptor zur behandlung von schmerzzuständen |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7300939B2 (ja) |
| EP (1) | EP1765816B1 (ja) |
| JP (1) | JP5022218B2 (ja) |
| AT (1) | ATE460413T1 (ja) |
| CA (1) | CA2572685A1 (ja) |
| CY (1) | CY1110127T1 (ja) |
| DE (2) | DE102004032567A1 (ja) |
| DK (1) | DK1765816T3 (ja) |
| ES (1) | ES2342473T3 (ja) |
| PL (1) | PL1765816T3 (ja) |
| PT (1) | PT1765816E (ja) |
| SI (1) | SI1765816T1 (ja) |
| WO (1) | WO2006002981A1 (ja) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102005062990A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
| DE102005062991A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7531529B2 (en) * | 2003-06-05 | 2009-05-12 | Roche Palo Alto Llc | Imidazole derivatives |
| EP2492265A1 (en) * | 2003-10-15 | 2012-08-29 | Sumitomo Chemical Company, Limited | 1,2,4-Thiadiazole Compounds and Pests Controlling Composition Containing the same |
| ES2307182T3 (es) | 2004-06-01 | 2008-11-16 | F. Hoffmann-La Roche Ag | Piridin-4-il-etinil-imidazoles y pirazoles como antagonistas receptores de mglur5. |
| EP2360588B1 (en) | 2005-03-16 | 2017-10-04 | III Holdings 12, LLC | Automatic workload transfer to an on-demand center |
| DE102005023784A1 (de) * | 2005-05-19 | 2006-11-30 | Grünenthal GmbH | Substituierte Spiro-Verbindungen und deren Verwendung zur Herstellung von Arzneimitteln |
| DE102005062986A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Propiolsäureamide und ihre Verwendung zur Herstellung von Arzneimitteln |
| US8541406B2 (en) | 2006-02-07 | 2013-09-24 | Nv Remynd | Thiadiazole derivatives for the treatment of neurodegenerative diseases |
| GB0602335D0 (en) * | 2006-02-07 | 2006-03-15 | Remynd Nv | Thiadiazole Derivatives For The Treatment Of Neurodegenerative Diseases |
| GB0623258D0 (en) | 2006-11-22 | 2007-01-03 | Remynd Nv | Thiadiazole derivatives for the treatment of neuro-degenerative diseases |
| EP2134687A1 (en) * | 2007-03-09 | 2009-12-23 | AstraZeneca AB | Piperazine and piperidine mglur5 potentiators |
| MX2010000351A (es) * | 2007-06-29 | 2010-05-17 | Acucela Inc | Compuestos derivados de alquinil fenilo para tratar enfermedades y desordenes oftalmicos. |
| EP2181110A2 (en) * | 2007-07-13 | 2010-05-05 | ADDEX Pharma S.A. | Novel heteroaromatic derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors |
| JP2012515214A (ja) | 2009-01-14 | 2012-07-05 | トヘ サルク インストイトウテ フオル ビオルオギクアル ストウドイエス | スクリーニング方法、及びアミロイド病に対し保護する化合物 |
| UY32940A (es) | 2009-10-27 | 2011-05-31 | Bayer Cropscience Ag | Amidas sustituidas con halogenoalquilo como insecticidas y acaricidas |
| EP2726470B1 (en) * | 2011-07-01 | 2015-04-29 | reMynd NV | 1,2,4-thiadiazol-5-ylpiperazine derivatives useful in the treatment of neurodegenerative diseases |
| AU2012296804B2 (en) * | 2011-08-17 | 2017-04-20 | Remynd Nv | Piperazine thiazole derivatives useful in the treatment of tauopathies such as alzheimer's disease |
| CN105837503A (zh) * | 2016-05-12 | 2016-08-10 | 蚌埠中实化学技术有限公司 | 一种6-溴喹啉的制备方法 |
| CN107325284B (zh) * | 2017-07-02 | 2020-01-14 | 苏州大学 | 一种超支化聚苯基三唑甲酸酯及其制备方法与应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0552418A1 (en) * | 1992-01-13 | 1993-07-28 | Takeda Chemical Industries, Ltd. | N-substituted-3-iodopropiolamide, production and use thereof |
| WO2001032690A1 (en) * | 1999-11-04 | 2001-05-10 | Fujisawa Pharmaceutical Co., Ltd. | Substituted dipeptides having nos inhibiting activity |
| WO2003093236A1 (en) * | 2002-05-02 | 2003-11-13 | Euro-Celtique, S.A. | 1-(pyrid-2-yl)-piperazine compounds as metabotropic glutamate receptor inhibitor |
| WO2004029044A1 (en) * | 2002-09-24 | 2004-04-08 | Euro-Celtique, S.A. | Pyrimidine compounds as therapeutic agents |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56120669A (en) * | 1980-02-27 | 1981-09-22 | Res Inst For Prod Dev | Allophanoylpiperazine compound and analgesic agent containing the same as active constituent |
-
2004
- 2004-07-05 DE DE102004032567A patent/DE102004032567A1/de not_active Withdrawn
-
2005
- 2005-07-05 EP EP05756539A patent/EP1765816B1/de not_active Not-in-force
- 2005-07-05 PL PL05756539T patent/PL1765816T3/pl unknown
- 2005-07-05 CA CA002572685A patent/CA2572685A1/en not_active Abandoned
- 2005-07-05 PT PT05756539T patent/PT1765816E/pt unknown
- 2005-07-05 SI SI200531017T patent/SI1765816T1/sl unknown
- 2005-07-05 JP JP2007519700A patent/JP5022218B2/ja not_active Expired - Fee Related
- 2005-07-05 DE DE502005009201T patent/DE502005009201D1/de active Active
- 2005-07-05 WO PCT/EP2005/007248 patent/WO2006002981A1/de active Application Filing
- 2005-07-05 AT AT05756539T patent/ATE460413T1/de active
- 2005-07-05 ES ES05756539T patent/ES2342473T3/es active Active
- 2005-07-05 DK DK05756539.2T patent/DK1765816T3/da active
-
2007
- 2007-01-04 US US11/649,156 patent/US7300939B2/en not_active Expired - Fee Related
-
2010
- 2010-06-03 CY CY20101100485T patent/CY1110127T1/el unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0552418A1 (en) * | 1992-01-13 | 1993-07-28 | Takeda Chemical Industries, Ltd. | N-substituted-3-iodopropiolamide, production and use thereof |
| WO2001032690A1 (en) * | 1999-11-04 | 2001-05-10 | Fujisawa Pharmaceutical Co., Ltd. | Substituted dipeptides having nos inhibiting activity |
| WO2003093236A1 (en) * | 2002-05-02 | 2003-11-13 | Euro-Celtique, S.A. | 1-(pyrid-2-yl)-piperazine compounds as metabotropic glutamate receptor inhibitor |
| WO2004029044A1 (en) * | 2002-09-24 | 2004-04-08 | Euro-Celtique, S.A. | Pyrimidine compounds as therapeutic agents |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102005062990A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
| DE102005062991A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
| US7871999B2 (en) | 2005-12-28 | 2011-01-18 | Gruenenthal Gmbh | Substituted thiazoles and their use for producing drugs |
| US8318774B2 (en) | 2005-12-28 | 2012-11-27 | Gruenenthal Gmbh | Compounds involving mGluR5 receptor regulation and methods of making the compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5022218B2 (ja) | 2012-09-12 |
| JP2008505149A (ja) | 2008-02-21 |
| SI1765816T1 (sl) | 2010-07-30 |
| DE502005009201D1 (de) | 2010-04-22 |
| PT1765816E (pt) | 2010-06-14 |
| DK1765816T3 (da) | 2010-06-14 |
| ATE460413T1 (de) | 2010-03-15 |
| CA2572685A1 (en) | 2006-01-12 |
| PL1765816T3 (pl) | 2010-08-31 |
| US20070112011A1 (en) | 2007-05-17 |
| ES2342473T3 (es) | 2010-07-07 |
| EP1765816A1 (de) | 2007-03-28 |
| WO2006002981A1 (de) | 2006-01-12 |
| US7300939B2 (en) | 2007-11-27 |
| CY1110127T1 (el) | 2015-01-14 |
| EP1765816B1 (de) | 2010-03-10 |
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| OM8 | Search report available as to paragraph 43 lit. 1 sentence 1 patent law | ||
| R005 | Application deemed withdrawn due to failure to request examination |
Effective date: 20110706 |